Figure 5.

Corneal nerves in health and in alkali-induced LSCD. (a) Schematic depiction of a healthy cornea, where stromal nerve trunks pass horizontally and occasionally deviate at right angles to pierce the BM and become ICBNs that course beneath and between basal corneal epithelia. Nerve fibers in suprabasal epithelial tiers terminate as free nerve endings. Functional interdependency between corneal nerves and epithelia are mediated by epitheliotropic and neurotropic factors. (b) Schematic depiction of alkali-induced LSCD with stromal nerve loss, diminished ICBN density, increased axon beading and tortuosity. Alkali-injured nerves release pro-inflammatory factors to stimulate leukocyte recruitment (neurogenic inflammation), while recruited leukocytes secrete pro-inflammatory cytokines that cause further nerve damage (neuroinflammation). (c,d) Images of mouse central cornea immunostained with rabbit anti-βIII-tubulin (Sigma-Aldrich, Burlington, Massachusetts, USA), the pan-neuronal marker. (c) In the healthy cornea, ICBNs form a typical whorl-like pattern. (d) LAB injury (see legend to Figure 1) causes profound loss of ICBNs and a change in ICBN morphology concomitant with loss of the whorl. Scale bars (c,d) represent 50 µm.